Notes

Short Record: Frequency involving Latent Rheumatic Heart Disease Between HIV-Infected Children in Kampala, Uganda.
Tomato, a widely consumed vegetable crop, offers a real potential to combat human nutritional deficiencies. Tomatoes are rich in micronutrients and other bioactive compounds (including vitamins, carotenoids, and minerals) that are known to be essential or beneficial for human health. This review highlights the current state of the art in the molecular understanding of the nutritional aspects, conventional and molecular breeding efforts, and biofortification studies undertaken to improve the nutritional content and quality of tomato. Transcriptomics and metabolomics studies, which offer a deeper understanding of the molecular regulation of the tomato's nutrients, are discussed. The potential uses of the wastes from the tomato processing industry (i.e., the peels and seed extracts) that are particularly rich in oils and proteins are also discussed. Recent advancements with CRISPR/Cas mediated gene-editing technology provide enormous opportunities to enhance the nutritional content of agricultural produces, including tomatoes. In this regard, genome editing efforts with respect to biofortification in the tomato plant are also discussed. The recent technological advancements and knowledge gaps described herein aim to help explore the unexplored nutritional potential of the tomato.
The growing prevalence of nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH), and its association with obesity as a metabolic disease contributes to harmful outcomes and healthcare resource burden worldwide. For this reason, there is an urgent need to develop new therapies. Identification of treatment targets, research design, endpoints definitions and assessments, and supportive regulatory pathways for drug approval all play prominent roles in shaping efforts in drug discovery, investigation, and approval.

In this perspective, the authors enumerate key challenges of NAFLD clinical research and offer a conceptual framework to address these issues which arise during clinical trials.

With the anticipated significant healthcare and costs burden that NAFLD will impose throughout the world, the diagnostics and drug development processes need to be accelerated. Important measures to improve clinical trial research include standardization of case definitions, comprehensive and granular covariate data collection, quality study development incorporating novel trial designs, and quality data reporting. The authors believe that these actions will accelerate understanding, development, and ultimately approval of efficacious treatments.
With the anticipated significant healthcare and costs burden that NAFLD will impose throughout the world, the diagnostics and drug development processes need to be accelerated. Important measures to improve clinical trial research include standardization of case definitions, comprehensive and granular covariate data collection, quality study development incorporating novel trial designs, and quality data reporting. The authors believe that these actions will accelerate understanding, development, and ultimately approval of efficacious treatments.Osteoarthritis (OA) is a major cause of disability worldwide with increasing age. Knee OA (KOA) is the most prevalent type of OA. Recently, it is considered that KOA is a whole joint disease, including articular cartilage, subchondral bone, synovium, ligaments, joint capsules, and muscles around the joint. Exosomes in knee joint are mainly secreted by articular chondrocytes and synoviocytes. They participate in cell and tissue cross-talk by carrying a complex cargo of proteins, lipids, nucleic acids, etc. Under normal conditions, exosomes maintain the microenvironmental homeostasis of the joint cavity. Under pathological conditions, the composition and function of exosomes changes, which in turn, disrupts the balance of anabolism and catabolism of articular chondrocyte and facilitates inflammatory responses, thus accelerating KOA progression. As a regenerative medicine, mesenchymal stem cells (MSCs) are promised to facilitate repair of degenerated cartilage and decelerate OA process. The therapeutic function of MSC mainly depends on MSC-derived exosomes, which can restore the homeostasis of the articular microenvironment. In the future, the specific mechanism of exosomes for OA treatment needs further elucidation, and the treatment effect of exosomes for long-term and/or severe OA needs further exploration.The transcription factor Pax4 plays an essential role in the development of insulin-producing β cells in pancreatic islets. Ectopic Pax4 expression not only promotes β cell survival but also induces α-to-β cell transdifferentiation. This dual functionality of Pax4 makes it an appealing therapeutic target for the treatment of insulin-deficient type 1 diabetes (T1D). In this study, we demonstrated that Pax4 gene delivery by an adenoviral vector, Ad5.Pax4, improved β cell function of mouse and human islets by promoting islet cell survival and α-to-β cell transdifferentiation, as assessed by multiple viability assays and lineage-tracing analysis. We then explored the therapeutic benefits of Pax4 gene delivery in the context of islet transplantation using T1D mouse models. Both mouse-to-mouse and human-to-mouse islet transplantation, via either kidney capsule or portal vein, were examined. In all settings, Ad5.Pax4-treated donor islets (mouse or human) showed substantially better therapeutic outcomes. These results suggest that Pax4 gene delivery into donor islets may be considered as an adjunct therapy for islet transplantation, which can either improve the therapeutic outcome of islet transplantation using the same amount of donor islets or allow the use of fewer donor islets to achieve normoglycemia.Long noncoding RNAs (lncRNAs) have been discovered to play a key role in adipogenesis, while the role of lncRNA human leukocyte antigen complex group 11 (HCG11) in adipocyte differentiation has not been studied clearly. We used human adipose-derived mesenchymal stem cells (hAdMSCs) to establish a model of cell differentiation in vitro and found that expression of lncRNA HCG11 was decreased during adipogenesis through real-time quantitative polymerase chain reaction analysis. Then, hAdMSCs were transfected with pcDNA-HCG11 or HCG11-shRNA (sh-HCG11); the adipogenic marker proteins were detected by Western blot, and the activity of lipogenesis enzymes was detected by spectrophotometry. The expression of CCAAT-enhancer-binding protein α, fatty acid-binding protein, peroxisome proliferator-activated receptor gamma 2 and the levels of acetyl coenzyme A carboxylase and fatty acid synthase FAS were significantly downregulated in hAdMSCs at different stages transfected with pcDNA-HCG11, while knockdown of lncRNA HCG11 promoted adipocyte differentiation. Bioinformatic analysis indicated that miR-204-5p was a potential target gene of HCG11, which was confirmed by luciferase reporter gene analysis and RNA pull-down analysis. In addition, miR-204-5p directly targeting the 3'-untranslated region of SIRT1 was also predicted by StarBase and verified by luciferase reporter gene analysis. Enforced expression of miR-204-5p negatively regulated the SIRT1 protein level. Furthermore, SIRT1 overexpression significantly inhibited adipogenic marker protein, levels of lipogenesis enzymes, and the proliferation of hAdMSCs. When pcDNA-HCG11 and miR-204-5p mimic were co-transfected into hAdMSCs, we found that the miR-204-5p mimic reversed the suppressor effect of pcDNA-HCG11. Taken together, we found that HCG11 negatively regulated cell proliferation and adipogenesis by the miR-204-5p/SIRT1 axis. Our findings might provide a new target for the study of adipogenesis in hAdMSCs and obesity.Bisphosphonates (BPs) are widely used to treat several metabolic and oncological diseases affecting the skeletal system. Despite BPs' well-known therapeutic potential, they also displayed important side effects, among which is BPs-related osteonecrosis of the jaw, by targeting osteoclast activities, osteoblast, and osteocyte behavior. The aim of this study is to evaluate the biological effects of zoledronic acid (ZOL) in an in vitro model of periodontal ligament stem cells (PDLSCs) by using an experimental setting that resembles the in vivo conditions. PDLSCs were treated with different concentrations of ZOL ranging from 0.1 to 5 μM. The effects of ZOL exposure were evaluated on cell viability via 3-[4,5-Dimethylthiaoly]-2,5-diphenyltetrazolium bromide (MTT), cell cycle analysis, apoptosis detection, and immunofluorescence. Quantitative real-time polymerase chain reaction (PCR), colorimetric detection of alkaline phosphatase activity, and Alizarin Red S staining were performed to investigate the osteogenic pocontrol cultures. In conclusion, chronic exposure to 1 μM ZOL induced significant reduction of osteogenic differentiation, while ZOL concentrations ≥1.5 μM are required to impair PDLSCs viability and induce apoptosis.Since 1973, Kunene River water has been carried from the Calueque reservoir in Angola along a 160 km open concrete canal to the town of Oshakati in the central part of the Cuvelai-Etosha Basin and has been supplying drinking water to the most densely populated rural area of Namibia. Despite its importance for the region, intra-seasonal water quality and the technical condition of the canal are not routinely checked. Water samples were collected during four field campaigns right before the onset of the rainy season (November 2013 and 2014), and after the rainy season (June 2014 and May 2015), at 16 sites along the canal for stable water isotopes (deuterium, oxygen-17 and oxygen-18) and hydrochemical analyses. The isotope patterns and chemical composition of the canal water is discussed in comparison to local rain, Kunene source water, surface water and groundwater. Clear isotope enrichment indicates evaporative loss of water. A Craig-Gordon model was used to estimate water loss. The loss increases with distance from the source with a maximum of up to 10 %, depending on the season. The results are discussed in context of water availability, vulnerability and water resources management in this water-scarce area.For over 60 years, warfarin has been the treatment of choice in the prevention of strokes and other thromboembolic events. In recent years, a new class of Novel Oral Anticoagulant (NOAC) medication has become available, leaving clinicians and health system payors to question whether warfarin continues to have a place in therapy. This article argues that it may not be the medication that should be in question but instead the systems in place to manage anticoagulation for the patients who need it. IDO-IN-2 purchase Usual Care (UC) for warfarin management has traditionally required multiple healthcare visits, blood collection visits, and laboratory analysis of International Normalized Ratio (INR) with results to then later be relayed to the patient along with dosage adjustments. The article reviews a new model of care, Community Pharmacist-led Anticoagulation Management Service (CPAMS), in which patients receive a point-of-care INR test along with a pharmacist assessment at a pharmacy and results within minutes. Pharmacists then prescribe dosage adjustments immediately, counsel patients, and provide supporting adherence tools such as a colourful picture-based dosing calendar, created by the decision support tool, INR Online.
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